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Sökning: WFRF:(Macken J)

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  • Underwood, J, et al. (författare)
  • Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
  • 2019
  • Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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  • Breugelmans, T., et al. (författare)
  • In-Depth Study of Transmembrane Mucins in Association with Intestinal Barrier Dysfunction During the Course of T Cell Transfer and DSS-Induced Colitis
  • 2020
  • Ingår i: Journal of Crohns & Colitis. - : Oxford University Press (OUP). - 1873-9946. ; 14:7, s. 974-994
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases [IBD] but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin expression is reported in the colon of IBD patients, we studied the association between mucin expression, inflammation and intestinal permeability in experimental colitis. Methods: We quantified 4-kDa FITC-dextran intestinal permeability and the expression of cytokines, mucins, junctional and polarity proteins at dedicated time points in the adoptive T cell transfer and dextran sodium sulfate [DSS]-induced colitis models. Mucin expression was also validated in biopsies from IBD patients. Results: In both animal models, the course of colitis was associated with increased interleukin-1 beta [IL-1 beta] and tumour necrosis factor-alpha [TNF-alpha] expression and increased Muc1 and Muc13 expression. In the T cell transfer model, a gradually increasing Muc1 expression coincided with gradually increasing 4-kDa FITC-dextran intestinal permeability and correlated with enhanced IL-1 beta expression. In the DSS model, Muc13 expression coincided with rapidly increased 4-kDa FITC-dextran intestinal permeability and correlated withTNF-alpha and Muc1 overexpression. Moreover, a significant association was observed between Muc1, Cldn1, Ocln, Par3 and aPKC zeta expression in the T cell transfer model and between Muc13, Cldn1, Jam2, Tjp2, aPkc zeta, Crb3 and Scrib expression in the DSS model. Additionally, MUC1 and MUC13 expression was upregulated in inflamed mucosa of IBD patients. Conclusions: Aberrantly expressed MUC1 and MUC13 might be involved in intestinal barrier dysfunction upon inflammation by affecting junctional and cell polarity proteins, indicating their potential as therapeutic targets in IBD.
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  • K Ljungberg, Jessica, et al. (författare)
  • Listen out! : Behavioural and subjective responses to verbal warnings
  • 2012
  • Ingår i: Applied Cognitive Psychology. - : John Wiley & Sons. - 0888-4080 .- 1099-0720. ; 26:3, s. 451-461
  • Tidskriftsartikel (refereegranskat)abstract
    • Both the behavioural and subjective impacts of single-word spoken warnings were examined. Behaviourally, the effect of infrequently occurring warnings was studied through their disruptive impact on a visually presented serial recall task. In separate experiments, ratings of the same words were elicited. Experiment 1 showed a localized effect of the warnings (on the item immediately following the warning), with the urgently intoned warning having a greater disruptive effect than its valence (emotional content). Valence and intonation (urgency) did not interact. The performance changes were mirrored in the ratings of the words. Experiment 2 showed no systematic effect on performance of either the action-relatedness of the word or its lexicality. There was, however, a systematic effect of lexicality but not action-relatedness on ratings. The study demonstrates the feasibility of using objective performance methods to establish the likely effects of verbal warnings and the utility of using such methods for the design of alarm systems.
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